Status and phase
Conditions
Treatments
About
This study will evaluate the safety and effectiveness of baricitinib in the treatment of giant cell arteritis. All participants will be taking prednisone at the start of the study. The prednisone will be reduced according to a standardized tapering schedule while participants continue to take one tablet of baricitinib daily for 52 weeks.
Full description
Baricitinib, an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2 has shown preliminary safety and efficacy in chronic, immune-mediated inflammatory conditions such as rheumatoid arthritis and psoriasis. This small molecule is uniquely suited as a potential novel therapeutic agent in GCA because of its suppressive effect on both the Th17 (IL-6, IL-23) andTh1 (IL-12, IFN-γ) pathways.
This study will evaluate the safety and tolerability of baricitinib in a population of patients with relapsing GCA. The study is an open-label pilot study assessing the safety and tolerability of baricitinib (4 mg daily, oral, for 52 weeks) in addition to a standardized glucocorticoid taper. It is anticipated that adjunct baricitinib will be safe and well tolerated by patients with GCA and demonstrate preliminary efficacy as measured by reducing inflammatory markers, decreasing steroid requirements and increasing relapse-free survival.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
Diagnosis of Giant Cell Arteritis (GCA) defined by the following Revised GCA Diagnosis Criteria:
Age ≥50 years.
History of Erythrocyte Sedimentation Rate (ESR) ≥ 50 mm/hour or C-Reactive Protein (CRP) ≥ 10 mg/L.
Presence of at least one of the following:
Presence of at least one of the following:
Relapse with active GCA within 6 weeks of study entry where active disease is defined by an ESR ≥30 mm/hr or CRP ≥10 mg/L AND the presence of at least one of the following:
Clinically stable at baseline visit (study drug initiation) such that the subject is able to safely participate in the standardized taper regimen in the opinion of the investigator.
Exclusion Criteria
Presence of any other autoimmune disease (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory arthritis, other vasculitides, scleroderma, polymyositis, dermatomyositis, or other similar systemic connective tissue diseases).
Subjects demonstrating symptoms of visual loss (transient or permanent blindness) or diplopia attributable to GCA.
Subjects with history of aortic dissection, myocardial infarction, or cerebrovascular attack attributable to GCA.
Has received, or is expected to receive, any live virus vaccinations (with the exception of herpes zoster vaccination) within 3 months before the first dose of study drug, during the study, or within 3 months after the last administration of the study drug. All patients who have not received the herpes zoster vaccine at screening will be encouraged (per local guidelines) to do so prior to randomization; vaccination must occur >4 weeks prior to randomization and start of investigational product. Patients will be excluded if they were exposed to herpes zoster vaccination within 4 weeks of planned randomization.
Organ transplant recipients.
Have had a major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator would pose an unacceptable risk to the patient.
Have experienced any of the following within 12 weeks of screening: myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure
Have a history or presence of cardiovascular (including but not limited to uncontrolled hypertension), respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders, or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to a wheelchair.
Have an estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73 m^².
Have a history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN) or the most recent available total bilirubin ≥1.5 times ULN (if available).
Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for < 5 years.
Active infections, or history of recurrent infections or have required management of acute or chronic infections as evidenced by any of the following:
Have had symptomatic herpes zoster infection within 12 weeks prior to screening.
Have a history of disseminated/complicated herpes zoster [for example, multidermatomal involvement, ophthalmic zoster or Central Nervous System (CNS) involvement]
In the opinion of the investigator, are at an unacceptable risk for participating in the study.
Have known or documented diagnosis of human immunodeficiency virus (HIV).
Have known or documented primary immunodeficiency.
Have had household contact with a person with active tuberculosis (TB) and did not receive appropriate and documented prophylaxis for TB.
Have had evidence of active TB or have previously had evidence of active TB and did not receive appropriate and documented treatment.
Have evidence of latent TB as documented by a local lab positive QuantiFERON®-TB Gold test and a normal chest x-ray, unless a patient completes at least 4 weeks of appropriate treatment prior to study entry and agrees to complete the remainder of treatment while in the trial.
Have a positive test for Hepatitis B Virus (HBV) defined as:
Have Hepatitis C Virus (HCV) (positive for anti-hepatitis C antibody with confirmed presence of HCV).
Have any of the following specific abnormalities on screening tests:
In the case of any of the aforementioned laboratory abnormalities, the tests may be repeated once within approximately 2 weeks from the initial values, and values resulting from repeat testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
Are pregnant or breast feeding at the time of screening or enrollment.
Are females of childbearing potential who do not agree to use 2 forms of highly effective birth control when engaging in sexual intercourse with a male partner while enrolled in the study and for at least 4 weeks following the last dose of the study drug
Females of non-childbearing potential are defined as women ≥60 years of age, women
≥40 but <60 years of age what had had cessation of menses for at least 12 months, or whom who are congenitally or surgically sterile (that is have had a hysterectomy, or bilateral oophorectomy or tubal ligation)
The following birth control methods are considered highly effective (the subject should choose 2 to be used with their male partner
i. Oral, injectable, or implanted hormonal contraceptives ii. Condom with spermicidal foam, gel film, cream or suppository iii. Occlusive cap (diaphragm or cervical/vault caps) with a spermicidal foam, gel, film, cream or suppository iv. . Intrauterine device v. Intrauterine system (for example progestin-releasing coil) vi. Vasectomies male (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)
Are males who do not agree to use 2 forms of highly effective birth control (see above) while engaging in sexual intercourse with females partners of childbearing potential while enrolled in the study and for 4 weeks after the last dose of the study drug.
Have donated more than a single unit of blood within 4 weeks prior to screening or intend to donate blood during the course of the study.
Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug above within the 2 years prior to screening.
Have previously received baricitinib for other investigational study.
Are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures
Are currently enrolled in, or discontinued within 4 weeks prior to screening from any other clinical trial involving an investigational product or nonapproved use of a drug or device or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling whether biological or legally adopted.
Have a chronic medical illness requiring the use of oral of IV glucocorticoid treatment (e.g. asthma or emphysema) during the trial or requiring long term glucocorticoid treatment such that they would not be able to safely undergone a standardized glucocorticoid taper.
Primary purpose
Allocation
Interventional model
Masking
15 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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